Use of assisted reproductive technology (ART) has risen steadily in the United States during the past two decades due to several reasons, including childbearing at older maternal ages and increasing insurance coverage. Studies have reported significantly higher risks of adverse perinatal outcomes in assisted- versus spontaneous-conception pregnancies, including an excess of prematurity, low birthweight, and birth defects. ART and/or infertility may influence the incidence of other conditions with prenatal origins, such as childhood cancer. In addition, the prevalence of imprinting disorders such as Beckwith-Wiedemann and Angelman syndromes is elevated among children conceived by ART;some of these disorders, in turn, drastically raise the risk of several embryonal cancers that occur in early childhood. Several cohort, case-control, and case- series studies of assisted reproduction and childhood cancer have reported null results, although all were limited by small sample size and could not differentiate specific cancer types. One study that focused specifically on hepatoblastoma found that use of infertility treatment or assisted reproduction was associated with a nine-fold increased risk of disease. Using the resources of the Society for Assisted Reproductive Technology (SART) and the birth and cancer registries in 20 States and New York City, we propose to conduct the largest study to date of ART and childhood cancer risk. SART maintains an ongoing national database of programs that provide ART services in the United States as mandated by the federal Fertility Success Rate and Certification Act of 1992 [PL 102-493]. As of 2006, the latest year of data available, this included comprehensive data (including identifiers sufficient for linkage) on 138,198 ART cycles from 483 clinics resulting in 41,343 pregnancies and 54,656 infants for a single year. We propose to link the data from the SART database from 2004-2013 to the birth and cancer registries of 20 states and New York City, including the five states with the highest numbers of ART births (California, New York, Illinois, New Jersey, and Massachusetts), to create a cohort of approximately 30 million children, including over 467,000 conceived by ART to evaluate the association between assisted reproduction and the risk for childhood cancer. The specific aim of this study is to compare the incidence of childhood cancer in children with assisted conception to that in the general population. PUBLIC HEALTH RELEVANCE: In this study we propose to link the data from the Society for Assisted Reproductive Technology national database from 2004-2013 to the birth and cancer registries of 19 states and New York City, to create a cohort of approximately 30 million children, including over 467,000 conceived by ART to evaluate the association between assisted reproduction and the risk for childhood cancer. The specific aim of this study is to compare the incidence of childhood cancer in children with assisted conception to that in the general population.